Systems, methods, and media for capsule-based multimode endoscopy

ABSTRACT

In some embodiments, systems, methods, and media for capsule-based multimode endoscopy are provided. In some embodiments, a probe for capsule-based multimode endoscopy is provided, the probe comprising: a rigid capsule; a flexible tether coupled to a proximal end of the capsule; a rotatable reflective surface disposed within the capsule; a static ball lens disposed within the capsule; a first optical fiber optically coupled to the ball lens, the first optical fiber passing through the flexible tether; a second optical fiber optically coupled to the ball lens, the second optical fiber passing through the flexible tether; a graded index fiber disposed between a distal end of the second optical fiber and the ball lens, the graded index fiber optically coupled to the second optical fiber and the ball lens.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.17/052,438, filed Nov. 2, 2020, which is a National Stage ofInternational Application No. PCT/US2019/030699, filed May 3, 2019,which is based on, claims the benefit of, and claims priority to U.S.Provisional Application No. 62/666,660, filed May 3, 2018, and entitled“TETHERED CAPSULE ENDOSCOPE ENDOMICROSCOPE.” The contents of each ofthese applications are hereby incorporated herein by reference in theirentirety for all purposes.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH

N/A

BACKGROUND

Gastrointestinal (GI) diseases are one of the most commonly reportedhealth care issues and a major contributor to the health care burdenwithin Unites States and worldwide. According to recent studies, therewere approximately 60 million ambulatory visits related to digestivedisorders, while GI-related healthcare costs are estimated to be upwardsof $140 billion annually. Endoscopy is often the primary diagnostic toolused in the GI tract, and must be performed under anesthesia usingconventional endoscopy techniques. Endoscopy is a major contributor toGI-related healthcare costs disease burden is endoscopy which. In 2012,an estimated 6.9 million upper GI endoscopies were performed with anestimated cost of $12.3 billion. The scale and impact of GI disorders onhealth care and health care costs are driving development of newtechnologies to aid standard white light imaging (WLI)-based endoscopyto better diagnose GI diseases, some of which can be performed withoutsedating the subject via anesthesia. Optical coherence tomography (OCT)has emerged a promising tool in this direction which provides real timevolumetric images of the whole GI tract at microscopic (e.g., on theorder of 30×30×10 micrometers (μm)) resolution compared to conventionalWLI-based endoscopy which only provides luminal surface images at amacroscopic level, which omits details of the underlying tissue.However, while OCT can provide microscopic information about thestructure of the tissue without anesthesia (e.g., via tethered capsuleOCT techniques), conventional OCT techniques cannot be used to generatevisible light images of the surface of the tissue. Such visible lightimages, which are generated via conventional WLI endoscopy, can oftenprovide more useful information than OCT for diagnosing certainconditions such as esophagitis, strictures, and/or ulcers.

Accordingly, devices, systems, and methods for capsule-based multimodeendoscopy are desirable.

SUMMARY

In accordance with some embodiments of the disclosed subject matter,devices, systems, and methods for capsule-based multimode endoscopy areprovided.

In accordance with some embodiments of the disclosed subject matter, aprobe is provided, the probe comprising: a rigid capsule; a flexibletether coupled to a proximal end of the capsule; a rotatable reflectivesurface disposed within the capsule; a static ball lens disposed withinthe capsule; a first optical fiber optically coupled to the ball lens,the first optical fiber passing through the flexible tether; a secondoptical fiber optically coupled to the ball lens, the second opticalfiber passing through the flexible tether; and a graded index fiberdisposed between a distal end of the second optical fiber and the balllens, the graded index fiber optically coupled to the second opticalfiber and the ball lens.

In some embodiments, the rotatable reflective surface is configured toreceive light emitted by the ball lens and direct the light toward acircumference of the rigid capsule.

In some embodiments, the probe further comprises a spacer disposedbetween the ball lens and the graded index fiber.

In some embodiments, the first optical fiber is a single mode fiber thatis configured to be optically coupled to an optical coherence tomographyimaging system.

In some embodiments, the second optical fiber is a dual clad fiber thatis configured to be optically coupled to a visible light imaging system.

In some embodiments, the graded index fiber has a length of between 100and 1,000 micrometers (μm).

In some embodiments, the ball lens has an axial diameter of between 0.1and 5 millimeters (mm).

In some embodiments, the probe further comprises a motor that ismechanically coupled to the rotatable reflective surface, and configuredto rotate the rotatable reflective surface.

In accordance with some embodiments of the disclosed subject matter, asystem for capsule-based multimode endoscopy is provided, the systemcomprising: a visible light imaging system comprising: a visible lightsource; and a visible light detector; an optical coherence tomography(OCT) imaging system comprising: an OCT light source; an OCT detector; asample arm optically coupled to the OCT light source and the OCTdetector; and a reference arm optically coupled to the OCT light sourceand the OCT detector, the reference arm comprising a referencereflector; and a probe comprising: a rigid capsule; a flexible tethercoupled to a proximal end of the capsule; a rotatable reflective surfacedisposed within the capsule; a static ball lens disposed within thecapsule; a first optical fiber optically coupled to the ball lens andthe sample arm of the OCT imaging system, the first optical fiberpassing through the flexible tether; a second optical fiber opticallycoupled to the ball lens and the visible light imaging system, thesecond optical fiber passing through the flexible tether; and a gradedindex fiber disposed between a distal end of the second optical fiberand the ball lens, the graded index fiber optically coupled to thesecond optical fiber and the ball lens.

In some embodiments, the system further comprises: at least oneprocessor that is programmed to: cause the rotatable reflective surfaceto rotate; cause the OCT light source to emit light toward the rotatablereflective surface via the first optical fiber; cause the visible lightsource to emit light toward the rotatable reflective surface via thesecond optical fiber; generate OCT data based on an interference betweenlight reflected from a sample and light reflected from the referencereflector; generate visible light image data based on light reflectedfrom a surface of the sample; and cause an image representing a firstportion of the sample based on the OCT data to be presentedsimultaneously with an image representing the first portion of thesample based on the visible light image data.

In some embodiments, the rotatable reflective surface is configured toreceive light emitted by the ball lens and direct the light toward acircumference of the rigid capsule.

In some embodiments, the probe further comprises a spacer disposedbetween the ball lens and the graded index fiber.

In some embodiments, the first optical fiber is a single mode fiber.

In some embodiments, the second optical fiber is a dual clad fiber, thecore of the dual clad fiber optically coupled to the visible lightsource and the cladding of the dual clad fiber optically coupled to thevisible light detector.

In some embodiments, the graded index fiber has a length of between 100and 1,000 μm.

In some embodiments, the ball lens has an axial diameter of between 0.1and 5 mm.

BRIEF DESCRIPTION OF THE DRAWINGS

Various objects, features, and advantages of the disclosed subjectmatter can be more fully appreciated with reference to the followingdetailed description of the disclosed subject matter when considered inconnection with the following drawings, in which like reference numeralsidentify like elements.

FIG. 1 shows an example of a system for capsule-based multimodeendoscopy in accordance with some embodiments of the disclosed subjectmatter.

FIG. 2 shows an example of a components that can be used to implement asystem for capsule-based multimode endoscopy in accordance with someembodiments of the disclosed subject matter.

FIG. 3A shows an example of optical components that can be used to focuslight from an OCT light source and a visible light source at a similarfocal length to implement a portion of a system for capsule-basedmultimode endoscopy in accordance with some embodiments of the disclosedsubject matter.

FIG. 3B shows an example of optical components that can be used to focuslight from an OCT light source and a visible light source at a similarfocal length implemented in accordance with some embodiments of thedisclosed subject matter.

FIG. 3C shows an example simulation of optical paths of light from anOCT light source and a visible light source emitted from opticsimplemented in accordance with some embodiments of the disclosed subjectmatter.

FIG. 3D shows different spot sizes for OCT light and visible light thatcan illuminate the sample in accordance with some embodiments of thedisclosed subject matter.

FIG. 4A shows an example of a tethered optical imaging probe that can beused in connection with systems for capsule-based multimode endoscopy inaccordance with some embodiments of the disclosed subject matter.

FIG. 4B shows another example of a tethered optical imaging probe thatcan be used in connection with systems for capsule-based multimodeendoscopy in accordance with some embodiments of the disclosed subjectmatter.

FIG. 4C shows an example of a tethered optical imaging probe implementedin accordance with some embodiments of the disclosed subject matter.

FIG. 5 shows an example of hardware that can be used to implement avisible light imaging device, an OCT imaging device, and/or a computingdevice that can be used in connection with some embodiments ofmechanisms for capsule-based multimode endoscopy in accordance with someembodiments of the disclosed subject matter.

FIG. 6 shows an example of a process for generating multimode image datain accordance with some embodiments of the disclosed subject matter.

FIG. 7A shows an example of a visible light image captured ex vivo ofswine mesenteric vessels generated using a conventional camera.

FIG. 7B shows an example of a visible light image captured ex vivo ofswine mesenteric vessels generated using a capsule-based multimodeendoscopy system implemented in accordance with some embodiments of thedisclosed subject matter.

FIG. 7C shows an example of enface OCT image data captured ex vivo ofswine mesenteric vessels generated using a capsule-based multimodeendoscopy system implemented in accordance with some embodiments of thedisclosed subject matter.

FIG. 7D shows an example of B-scan OCT image data captured ex vivo ofswine mesenteric vessels generated using a capsule-based multimodeendoscopy system implemented in accordance with some embodiments of thedisclosed subject matter.

FIG. 8A shows an example of a visible light image captured in vivo ofswine esophagus generated using a capsule-based multimode endoscopysystem implemented in accordance with some embodiments of the disclosedsubject matter.

FIG. 8B shows an example of cross-sectional OCT image data captured invivo of swine esophagus generated using a capsule-based multimodeendoscopy system implemented in accordance with some embodiments of thedisclosed subject matter.

DETAILED DESCRIPTION

In accordance with some embodiments of the disclosed subject matter,mechanisms (which can include devices, systems, and methods) forcapsule-based multimode endoscopy are provided.

In accordance with some embodiments of the disclosed subject matter,mechanisms for generating OCT and visible light image data substantiallysimultaneously can be provided. In some embodiments, such mechanisms canreduce a subject's discomfort, reduce procedure time, and facilitatepost procedure image co-registration for OCT and visible light images.Previous attempts have been made to combine a mini color camera alongand rotating OCT optics inside a tethered capsule. However, thisarrangement suffers from complications such as non-uniform rotationaldistortion in the OCT data, and a mismatch in perspective between aforward-facing color camera and the circumferential OCT imagingmodality, which cause difficulties co-registering images obtained withboth modalities. In some embodiments, the mechanisms described hereincan facilitate generation of OCT and visible light images (e.g., of theupper GI tract) that feature a similar perspective and can more easilybe spatially and temporally co-registered.

FIG. 1 shows an example 100 of a system for capsule-based multimodeendoscopy in accordance with some embodiments of the disclosed subjectmatter. As shown in FIG. 1 , system 100 can include a capsule 102mechanically coupled to a tether 104. As described below in connectionwith FIGS. 3A, and 4A to 4C, capsule 102 can include optical componentsthat are configured to direct light received via tether 104 toward acircumference of capsule 102, such that the light is directed toward asurface of a subject's organ, such as the esophagus or another portionof the subject's GI tract.

In some embodiments, a visible light imaging device 106 can be opticallycoupled to capsule 102 via an optical waveguide 108 (e.g., an opticalfiber). In some embodiments, visible light imaging device 106 can emitvisible light at one or more wavelengths toward a proximal end ofoptical waveguide 108, which can convey the visible light to one or moreoptical components in capsule 102. In some embodiments, the one or moreoptical components in capsule 102 can cause the visible light to bedirected toward a circumference of capsule 102 and onto a surface of asubject's organ (e.g., after the subject has swallowed capsule 102). Aportion of the visible light can be reflected by the surface of thesubject's organ back toward capsule 102. In some embodiments, one ormore optical components in capsule 102 can direct the reflected lightback toward a distal end of optical waveguide 108, which can convey thereflected light back to visible light imaging device 106. In someembodiments, visible light imaging device 106 can include one or moredetectors that can be used to detect visible light returned from capsule102, and one or more processors (e.g., included in visible light imagingdevice or in another device) can generate visible light image data basedon the visible light detected by visible light imaging device.

In some embodiments, an OCT imaging device 110 can be can be opticallycoupled to capsule 102 via an optical waveguide 112 (e.g., an opticalfiber). In some embodiments, OCT imaging device 110 can emit light atone or more wavelengths suitable or OCT imaging (e.g., infrared light,near-infrared light) toward a proximal end of optical waveguide 112,which can convey the light to one or more optical components in capsule102. In some embodiments, the one or more optical components in capsule102 can cause the light to be directed toward a circumference of capsule102 and toward a surface of a subject's organ (e.g., after the subjecthas swallowed capsule 102). A portion of the light can be reflected atvarious depths from the surface of the subject's organ to severalmillimeters (e.g., on the order of 3-4 mm) below the surface of thesubject's organ back toward capsule 102. In some embodiments, one ormore optical components in capsule 102 can direct the reflected OCTlight back toward a distal end of optical waveguide 112, which canconvey the reflected OCT light back to OCT imaging device 110. In someembodiments, OCT imaging device 110 can include one or more detectorsthat can be used to detect OCT light returned from capsule 102, and oneor more processors (e.g., included in visible light imaging device or inanother device) can generate OCT image data based on the visible lightdetected by visible light imaging device 106. As described below inconnection with FIG. 2 , a portion of the light emitted by OCT imagingdevice 110 can be directed to a reference arm with a reflector that ispositioned at approximately the same distance from the one or moredetectors as the sample (e.g., the surface of the subject's organ) to beimaged.

In some embodiments, a computing device 114 can be coupled to visiblelight imaging device 106 and/or OCT imaging device 110, and can beconfigured to process, display, and/or store image data generated byvisible light imaging device 106 and/or OCT imaging device 110 in realtime. In some embodiments, computing device 114 can control and/orcoordinate operation of visible light imaging device 106 and/or OCTimaging device 110. In some embodiments, computing device 114 can beconfigured to communicate with visible light imaging device 106 and/orOCT imaging device 110 using any suitable technique or combination oftechniques, such as via wired links (e.g., Ethernet, USB, etc.) and/orwireless links (e.g., Wi-Fi, Bluetooth, etc.).

FIG. 2 shows an example 200 of a components that can be used toimplement a system for capsule-based multimode endoscopy in accordancewith some embodiments of the disclosed subject matter. As shown in FIG.2 , visible light imaging device 106 can include one or more visiblelight sources 202 and one or more visible light detectors 204, eachoptically coupled to a fiber coupler 206 (e.g., a dual clad fibercoupler), in some embodiments. In some embodiments, visible lightsource(s) 202 can be optically coupled to a port of fiber coupler 206using a dual clad fiber, and visible light detector(s) 204 can beoptically coupled with a second port of fiber coupler 206 using anoptical fiber (e.g., a single mode fiber, dual clad fiber, or amultimode fiber). In one particular example, a multimode fiber can befused to a dual clad fiber provided at a port of the fiber coupler 206.In some embodiments, a dual clad fiber (sometimes referred to as adouble clad fiber) can be used to optically couple a third port of fibercoupler 206 with one or more optical components within probe 102 (e.g.,as described below in connection with FIG. 3A). Note that, in someembodiments, an optical circulator can be used in lieu of fiber coupler206, with a first port optically coupled to visible light source(s) 202,a second port optically coupled to one or more optical components withincapsule 102, and a third port optically coupled to visible lightdetector(s) 204.

In some embodiments, one or more processors 208 can be electricallycoupled to visible light source(s) 202 and/or visible light detector(s)204, and can be configured to control operation of visible lightsource(s) 202, visible light detector(s) 204, and/or any othercomponents of visible light imaging device 106. Additionally, in someembodiments, processor 208 can be configured to process and/or outputimage data generated using visible light detector(s) 204.

In some embodiments, visible light source(s) 202 can be any suitablelight source that can be used to generate visible light image data. Forexample, in some embodiments, visible light source(s) 202 can beimplemented using a broadband white light source. In some embodiments,any suitable light source or combination of light sources can be used toimplement visible light source(s) 202, such as a filament-based lightsource, one or more conventional light emitting diodes (LEDs), one ormore superluminescent LEDs (SLED), one or more superluminescent diodes(SLD), one or more plasma light sources, one or more supercontinuumlight sources, one or more femtosecond lasers. As another example,visible light source(s) 202 can be implemented using multiple visiblelight sources, such as a green light source, a red light source, and ablue light source, which can be activated simultaneously orintermittently. In a more particular example, a first light source(e.g., a green light source) can be activated for a period of timecorresponding to a particular number of revolutions of optics withincapsule 102, a second light source (e.g., a red light source) can beactivated for a period of time corresponding to a successive particularnumber of revolutions of optics within capsule 102, and so on.

In some embodiments, visible light detector(s) 204 can be any suitablevisible light detector(s) that can be used to generate visible lightimage data. For example, in some embodiments, visible light detector(s)204 can be implemented using a CCD or CMOS sensor that receives lightreflected from the sample (e.g., via a multimode fiber optically coupledto fiber coupler 206), and converts the reflected light into image data.In some embodiments, visible light detector(s) 204 can include an arrayof detector elements (e.g., a linear array of pixels, a two dimensionalarray of pixels), and one or more optical components can be used tocause light reflected from the sample to be directed to differentportions of the array. For example, the reflected light can be spreadacross the array using a negative lens that receives light emitted froman optical fiber and cause the received light to diverge from the lens.In such an example, different pixels in the array can be associated withfilters having different wavelengths such that the amount of lightreflected from the sample at each of the different wavelengths can bemeasured. As another example, the reflected light can be spread acrossthe array using a grating or other spectral dispersion element (e.g., aprism) that directs different wavelengths of light toward differentportions of the array. In such an example, different pixels in the arraycan be associated with different wavelengths based on the spatialrelationship between the position of the pixel and the spectraldispersion element such that the amount of light reflected from thesample at each of the different wavelengths can be measured. As yetanother example, the reflected light can be input to a fiber-basedwavelength division multiplexor (WMD) that outputs light at differentwavelengths from different optical fibers. In such an example, differentpixels in the array can be associated with different optical fibers, andhence different wavelengths, such that the amount of light reflectedfrom the sample at each of the different wavelengths can be measured. Asanother example, visible light detector(s) 204 can be implemented usingone or more monochromatic visible light pixels (e.g., having an IR cutfilter, but not having a color filter) configured to detect light thatreturns to visible light detector(s). In such an example, visible lightsource(s) 202 can be configured to output a single color for aparticular period of time, and processor 208 can assign colorinformation to the image data based on the time at which the image datawas generated.

In some embodiments, OCT imaging device 110 can include one or more OCTlight source(s) 212 and one or more OCT detector(s) 214. In someembodiments, OCT light source(s) 202 can be optically coupled to a portof a beam splitter 216 using a single mode fiber, and output ports ofbeam splitter 216 can each be optically coupled to a first port ofoptical circulators 220 and 222 using single mode fibers. In someembodiments, beam splitter 216 can direct any suitable portion of thelight received from OCT light source(s) 212 toward the sample arm andreference arm. For example, beam splitter 216 can direct 90% if thelight received from OCT light source(s) 212 toward the sample arm and10% toward the reference arm.

In some embodiments, optical circulator 220 can be integrated into asample arm, in which a second port of optical circulator 220 isoptically coupled to one or more optical components in capsule 102 via asingle mode fiber, which can convey light emitted by OCT light source(s)212 to capsule 102 and convey light from a sample back from capsule 102to the second port of optical circulator 220.

In some embodiments, optical circulator 222 can be integrated into areference arm, in which a second port of optical circulator 222 isoptically coupled via a length of optic waveguide 224 (e.g., single modefiber) that can be configured to delay light from optical circulator 222such that the length of the reference arm is substantially similar to alength of the sample arm (e.g., similar on the order of the rangingdepth, such as from 0 to 10 mm). In some embodiments, optics 226 can beused to direct a beam of light toward a reference reflector 228, and tocollect light reflected from reference reflector 228. In someembodiments, optics 226 and/or reference reflector can be actuated tochange the length of the reference arm.

In some embodiments, light reflected by the sample can be received atthe second port of optical circulator 220 and light reflected byreference reflector 228 can be received at the second port of opticalcirculator 222, and the third port of each optical circulator 220 and222 can be optically coupled to a beam splitter 230, that is opticallycoupled to one or more OCT detector(s) 214.

In some embodiments, one or more processors 218 can be electricallycoupled to OCT light source(s) 212 and/or OCT detector(s) 214, and canbe configured to control operation of OCT light source(s) 212, OCTdetector(s) 214, and/or any other components of OCT imaging device 110.Additionally, in some embodiments, processor 218 can be configured toprocess and/or output OCT data generated using OCT detector(s) 214.

In some embodiments, OCT light source(s) 212 can be any suitable lightsource that can be used to generate OCT data. For example, in someembodiments, OCT light source(s) 212 can be implemented using a sweptsource laser. As another example, a polychromatic light source can beused to implement OCT light source(s) 212. As yet another example, abroadband light source can be used to implement OCT light source(s) 212.As still another example, a frequency comb light source can be used toimplement OCT light source(s) 212. Note that different OCT imagingtechniques can be used for different types of light source. For example,optical frequency domain imaging (OFDI) OCT techniques can be used witha swept source, while spectral-domain OCT (SD-OCT) techniques can beused with a frequency comb source. In a more particular example, OCTlight source(s) 212 can be implemented using a Swept Source Engine fromAXSUN Technologies (of Billerica, Mass.), which can include a sweptlaser that sweeps over a range of about 50-200 nm (e.g., a range of 50nm, 75 nm, 100 nm, 125 nm, 150 nm, 175 nm, 200 nm, or any other suitablerange) centered in the infrared or near infrared (e.g., 850 nm, 1060 nm,1220 nm, 1310 nm, 1700 nm, or any other suitable wavelength) at afrequency of about 50 kilohertz (kHz) to 200 kHz (e.g., 50 kHz, 75 kHz,100 kHz, 125 kHz, 150 kHz, 175 kHz, 200 kHz, or any other suitablefrequency). In some embodiments, the spectral width can be on the orderof 0.1 to 1 angstrom.

In some embodiments, OCT detector(s) 214 can be any suitable detector(s)that can be used to generate OCT data. For example, in some embodiments,OCT detector(s) 214 can be implemented using one or more CCD or CMOSsensors that receive light reflected from the sample (e.g., via one ormore single mode fibers optically coupled to beam splitter 230), andconvert the reflected light into OCT data. In some embodiments, sampleand reference signals interfere with each other at beam splitter 230. Insome such embodiments, multiple outputs of beam splitter 230 can each becoupled to a polarization beam splitter via a single mode fiber coupledto one or more polarization controllers and polarization maintainingfiber to implement a polarization diverse detection scheme that canavoid image artifacts due to polarization changes induced by the opticalfiber in catheter 104. In some embodiments, light from the polarizationmaintaining fibers can be detected using two balanced detectors composedof four photodiode receivers (e.g., each supplied by an output of apolarization beam splitter). The digitized signal from the photodiodescan then be processed using a field-programmable gate array (FPGA) orapplication specific integrated circuit (ASIC) board includingwavelength re-mapping and Fourier transformation to obtain adepth-resolved OCT signal (sometimes referred to as an A-line). In someembodiments, regardless of how the A-lines are generated, the A-linescan be collected during every rotation of the optical beam andcompressed to a jpeg format and transferred using an Ethernet cable to aworkstation (e.g., computing device 114), for real-time display and/ordata storage. Note that this is merely an example, and other detectiontechniques and/or processing techniques can be used to generate OCTdata. For example, a single detector can be used to detect aninterference pattern between light from the sample arm and the referencearm. As another example, one or more common path interferometrytechniques in which the reference arm and sample arm travelsubstantially the same path (e.g. the reference reflector can be locatedwithin capsule 102). As yet another example, one or more polarizationdiversity detection techniques can be used. As still another example,one or more SD-OCT techniques can be used in which different pixels inthe detection array are configured to detect light at a differentwavelength (e.g., light can be directed across the array using aspectral dispersion element). In some embodiments, one or more filterscan be used to inhibit OCT light from reaching visible light detector(s)and vice versa. For example, bulk optical filters can be used to inhibitlight in unwanted wavelengths from reaching the detectors. As anotherexample, a fiber-based WMD can be used to divert light at an undesirablewavelength(s) from reaching the detector(s).

FIG. 3A shows an example 300 of optical components that can be used tofocus light from an OCT light source and a visible light source at asimilar focal length to implement a portion of a system forcapsule-based multimode endoscopy in accordance with some embodiments ofthe disclosed subject matter. As shown in FIG. 3A, one or more opticalcomponents can be used to focus light emitted by one or more visiblelight sources (e.g., visible light source(s) 202) and/or one or more OCTlight sources (e.g., OCT light source(s) 212). In some embodiments,optics 300 can include a ball lens 302 that can be optically coupled toan OCT light source(s) via a single mode fiber 304. Note that this ismerely an example, and other suitable types of focusing elements orcombination of elements can be used such as a gradient-index (GRIN)lens, an aspheric lens, a Fresnel lens, etc. For example, single modefiber 304 can have a diameter of roughly 125 μm (e.g., the conventionalcladding can have an external diameter of roughly 125 μm surrounding acore having a diameter in the range of about 4 to 10 μm, although thecladding can have other diameters, such as in the range of 60-250 μm).Additionally, in some embodiments, ball lens 302 can be opticallycoupled to a visible light source(s) via a dual clad fiber 306 and aportion of graded index (GRIN) fiber 308 that can serve to narrow thebeam of visible light emitted by dual clad fiber 306. For example, dualclad fiber 306 can have a diameter of roughly 125 μm. (e.g., the outerlayer of cladding can have an external diameter of roughly 125 μmsurrounding an inner layer of cladding and a core having a diameter inthe range of about 4 to 10 μm, although the outer cladding can haveother diameters, such as in the range of 60-250 μm) As another example,GRIN fiber 308 can have a length in the range of about 0.1 to 5 mm(e.g., a length of about 100 μm, 150 μm, 200 μm, 250 μm, etc.) or longer(e.g., a maximum rigid length of the probe, such as 1 centimeter). Notethat the GRIN fiber can confine the signal, and can be configured tohave a length that causes the visible light to exit the GRIN fiber witha beam width that will cause an appropriate beam size at the surface ofthe sample (e.g., to provide an appropriate lateral resolution for colorimaging). In some embodiments, various factors can be considered whensetting the length of the GRIN lens, such as the index of refraction ofthe focusing element (e.g., the material used to make a ball lens thatis used to focus the visible and OCT light) as the index refractionaffects the radius of curvature needed to provide a given focal length,which can affect the length of the GRIN fiber needed to output thevisible light at an appropriate beam size. In some embodiments, the GRINfiber provide different focusing properties for the different types oflight, such that when the light that passes through the GRIN fiber isfocused by the same element (e.g., ball lens) as the light that did notpass through the GRIN fiber the light emitted by the focusing elementhas different properties. For example, the GRIN fiber can reduce thenumerical aperture for the visible light and facilitate extension of thedepth of focus for the visible light. As another example, the GRIN fibercan cause the visible light to have an increased depth of focus (e.g.,an eight fold increase in the depth of focus that can be achieved forvisible light), which can cause the visible light to impinge the surfaceof the sample with much larger spot size. This can facilitate colorimaging with a resolution appropriate for generating visible lightimages comparable to images captured by a conventional digital camera,while facilitating OCT imaging with a resolution appropriate formicroscopic imaging of the internal structure of the sample. In someembodiments, light (both visible light and OCT light) reflected by thesample can be focused by the ball lens, and OCT light can be returned toa OCT detector(s) (e.g., OCT detector(s) 214) via the single mode fiber,while a cladding of the dual clad fiber can be used to return light to avisible light detector(s) (e.g., visible light detector(s) 204).

In some embodiments, a spacer 310 can be disposed between ball lens 302and the fibers (e.g., single mode fiber 304, and dual clad fiber306/GRIN fiber 308). In some embodiments, spacer 310 can have anysuitable diameter, and can allow beams of the OCT light and visiblelight to expand, which can facilitate an increase in the depth of focus.For example, spacer 310 an have a diameter in the range of about 0.1 to5,000 μm, which can remain constant over the length of the spacer or canchange along the length of the spacer (e.g., the diameter of the spacercan increase from a proximal end optically coupled to the fibers to adistal end optically coupled to/forming part of the focusing element).In a more particular example, the spacer can have a diameter of about 1mm. As another example, ball lens 302 can have a diameter in the rangeof about 0.5 to 5 mm. In a more particular example, ball lens 302 canhave a diameter of about 2.5 mm. Note that, one or both beams may be atleast slightly off axis with respect to the optical axis of spacer 310and/or ball lens 302. For example, single mode fiber 304 can be locatedon axis, while dual clad fiber/GRIN fiber 308 can be located slightlyoff axis. However, any negative effects can be mitigated, for example bya relatively low numerical aperture of the visible light optics. Asanother example, any positional errors caused by the fiber(s) being offaxis remain consistent during scanning and accordingly can have arelatively small effect on the accuracy of the visible light and/or OCTimage data.

FIG. 3B shows an example of optical components that can be used to focuslight from an OCT light source and a visible light source at a similarfocal length implemented in accordance with some embodiments of thedisclosed subject matter. As shown in FIG. 3B, a ball lens and spacerwere implemented and optically coupled to a tether that included asingle mode fiber, a dual clad fiber, and a GRIN fiber disposed betweenthe spacer and the dual clad fiber (e.g. as shown diagrammatically inFIGS. 3A and 3C).

FIG. 3C shows an example simulation of optical paths of light from anOCT light source and a visible light source emitted from opticsimplemented in accordance with some embodiments of the disclosed subjectmatter. As shown in the simulation, the OCT light may initially have awider beam than the visible light, but the focal point at can be locatedroughly the same distance from the ball lens, and the more aggressivefocusing provided father from the optical axis of ball lens 302 cancause the OCT beam to have a narrower beam (and a smaller depth offocus) when it reaches the focal point (e.g., at or near the surface ofthe sample). As described below, FIG. 3D shows an example of differentspot sizes at the focal point for OCT light and visible light, which canprovide different lateral resolution (e.g., a more detailed microscopicresolution for the OCT light and a less detailed more macroscopicresolution for the visible light).

FIG. 4A shows an example 400 of a tethered optical imaging probe thatcan be used in connection with systems for capsule-based multimodeendoscopy in accordance with some embodiments of the disclosed subjectmatter. As shown in FIG. 4A, imaging probe 400 can include a capsule 102and a tether 104 coupled to a proximal end 402 of capsule 102. In someembodiments, capsule 102 can have dimensions that facilitate swallowingby a subject, which can be in certain cases, be a human subject such asan adult or a child, and which can be in other cases, a veterinarysubject. In some embodiments, capsule 102 can define a generallycylindrical shape with hemispherical ends with a capsule diameter D anda capsule length L. For example, the capsule diameter D can be betweenapproximately 5 mm and approximately 20 mm. As another example, thecapsule diameter D can be between approximately 10 mm and approximately15 mm. As yet another example, the capsule length L can be betweenapproximately 20 mm and approximately 30 mm. As still another example,the capsule length L can be between approximately 22 mm andapproximately 28 mm.

In some embodiments, capsule 102 can be fabricated from a biocompatiblematerial configured to efficiently transmit light reflected from areflective surface 404 through capsule 102 onto a sample, and toefficiently transmit light reflected from the sample through capsule 102onto the reflective surface 404. In some non-limiting examples, capsule102 can be fabricated from PMMA in combination with other plastics ormetals such as stainless steel or brass.

In some embodiments, tether 104 can include optical waveguides 108 and112 (e.g., single mode fiber 304 and dual clad fiber 306). Additionally,in some embodiments, the configuration of the tethered optical imagingprobe 400 can negate the need to rotate the optics within tether 104.For example, tether 104 can define a substantially reduced diameter whencompared to a sheath used with other technique, and does not need to befabricated from low-friction materials to compensate for a rotatingoptical fiber. Accordingly, tether 104 can provide more flexibility anda substantially reduced cost (e.g., on the order of a few cents to a fewdollars compared to —$200 when compared to a tether used with somerotating optical fiber-based techniques). In some embodiments, tether104 can be fabricated from a biocompatible material (e.g., Polyimide,Pebax, PTFE, FEP).

In some embodiments, a motor 406 can be mechanically coupled toreflective surface 404, and both can be enclosed within capsule 104. Insome embodiments, motor 406 can include a drive shaft 408 that rotatablycouples reflective surface 404 to motor 406. In operation, as motor 406rotates drive shaft 408, reflective surface 404 rotates with drive shaft408. In the example shown in FIG. 4A, motor 406 can be powered by apower supply 410 arranged within capsule 102 near a distal end 412 ofcapsule. In some embodiments, power supply 410 can be implemented as abattery, a rechargeable battery, a solar cell, and/or any other suitablepower supply components or combination of power supply components. Insome embodiments, a controller (not shown) can be configured towirelessly communicate with motor 406.

In some embodiments, motor 406 can be arranged within capsule 104 suchthat drive shaft 408 extends toward distal end 402 of capsule 102,thereby arranging the reflective surface 404 rotatably coupled theretoadjacent to ball lens 302. In some embodiments, motor 404 utilized inthe tethered optical imaging probe 400 can be disposable and low-cost(e.g., between —$1 and $10). For example, motor 404 can be a motortypically used to generate vibrations in a mobile device such as asmartphone. Techniques for controlling such a low-cost motor aredescribed in U.S. Patent Application Publication No. 2018/0160965, whichis hereby incorporated by reference herein in its entirety.

In some embodiments, drive shaft 408 of motor 406 can be associated witha damping weight 414 coupled thereto for rotation therewith, which canreduce short-term fluctuations in a rotational speed of motor 406 byincreasing a moment of inertia. Additionally, in some embodiments,damping weight 414 can define a generally cylindrical shape, and can bemade from any suitable material or combination of materials (e.g.,brass). For example, damping weight 414 can define a weight of betweenapproximately 0.01 grams (g) and 4 g.

FIG. 4B shows another example 450 of a tethered optical imaging probethat can be used in connection with systems for capsule-based multimodeendoscopy in accordance with some embodiments of the disclosed subjectmatter. In some embodiments, tethered optical imaging probe 450 can besimilar to tethered optical imaging probe 400 of FIG. 4A, but can beimplemented using one or more wires that pass through tether 104. Asshown in FIG. 4B, tethered optical imaging probe 450 includes one ormore wires 452 extending into and along capsule 102. Each of the wires452 can be coupled to a corresponding terminal 454 of motor 406.

In some embodiments, a power supply can be arranged externally fromcapsule 102, and the power supply can be in communication with acontroller. For example, the controller can be in wired or wirelesscommunication with the power supply, and/or the controller can includean integrated power supply.

FIG. 4C shows an example of a tethered optical imaging probe implementedin accordance with some embodiments of the disclosed subject matter. Asshown in FIG. 4C, a tethered capsule was implemented that incorporatedoptics similar to the optics shown in FIG. 3A in a capsule having awired motor that controls rotation of a reflector (e.g., a reflectiveprism).

FIG. 5 shows an example 500 of hardware that can be used to implement avisible light imaging device, an OCT imaging device, and/or a computingdevice that can be used in connection with some embodiments ofmechanisms for capsule-based multimode endoscopy in accordance with someembodiments of the disclosed subject matter. For example, hardware shownin FIG. 5 can be used to implement at least a portion of system 100. Asshown in FIG. 5 , in some embodiments, a color imaging system (e.g.,visible light imaging device 106) can include a hardware processor 208,a user interface and/or display 504, one or more communication systems506, memory 508, one or more visible light sources 510, one or moreelectromagnetic detectors 512, and/or one or more optical connectors514. In some embodiments, hardware processor 208 can be any suitablehardware processor or combination of processors, such as a centralprocessing unit (CPU), a graphics processing unit (GPU), amicrocontroller (MCU), an FPGA, an ASIC, a dedicated image processor,etc. In some embodiments, input(s) and/or display 504 can include anysuitable display device(s), such as a computer monitor, a touchscreen, atelevision, a transparent or semitransparent display, a head mounteddisplay, etc., and/or input devices and/or sensors that can be used toreceive user input, such as a keyboard, a mouse, a touchscreen, amicrophone, a gaze tracking system, motion sensors, etc. Note that, insome embodiments, input(s)/display 504 can be omitted, such asembodiments in which operations of color imaging system 110 iscontrolled by computing device 114.

In some embodiments, communications systems 506 can include any suitablehardware, firmware, and/or software for communicating information over acommunication network 502 and/or any other suitable communicationnetworks. For example, communications systems 506 can include one ormore transceivers, one or more communication chips and/or chip sets,etc. In a more particular example, communications systems 506 caninclude hardware, firmware and/or software that can be used to establisha Wi-Fi connection, a Bluetooth connection, a cellular connection, anEthernet connection, an optical connection, etc.

In some embodiments, communication network 502 can be any suitablecommunication network or combination of communication networks. Forexample, communication network 502 can include a Wi-Fi network (whichcan include one or more wireless routers, one or more switches, etc.), apeer-to-peer network (e.g., a Bluetooth network), a cellular network(e.g., a 3G network, a 4G network, etc., complying with any suitablestandard, such as CDMA, GSM, LTE, LTE Advanced, WiMAX, etc.), a wirednetwork, etc. In some embodiments, communication network 502 can be alocal area network, a wide area network, a public network (e.g., theInternet), a private or semi-private network (e.g., a corporate oruniversity intranet), any other suitable type of network, or anysuitable combination of networks. Communications links shown in FIG. 5can each be any suitable communications link or combination ofcommunications links, such as wired links, fiber optic links, Wi-Filinks, Bluetooth links, cellular links, etc.

In some embodiments, memory 508 can include any suitable storage deviceor devices that can be used to store instructions, values, etc., thatcan be used, for example, by hardware processor 208 to process imagedata generated by one or more optical detectors, to present contentusing input(s)/display 504, to communicate with computing device 114 viacommunications system(s) 506, etc. Memory 508 can include any suitablevolatile memory, non-volatile memory, storage, any other suitable typeof storage medium, or any suitable combination thereof. For example,memory 508 can include RAM, ROM, EEPROM, one or more flash drives, oneor more hard disks, one or more solid state drives, one or more opticaldrives, etc. In some embodiments, memory 508 can have encoded thereon acomputer program for controlling operation of color imaging system 106.In some such embodiments, hardware processor 208 can execute at least aportion of the computer program to control one or more light sourcesand/or detectors (e.g., to capture visible light image data as describedabove in connection with FIG. 2 ), to generate images and/or calculatevalues (e.g., a visible light image, etc.), transmit and/or receiveinformation to/from computing device 114, combine visible light imagesfrom different color channels to generate multi-colored images, etc.

In some embodiments, imaging system 106 can include one or more lightsources 510, such one or more coherent or incoherent light sources(e.g., light emitting diodes or combination of light emitting diodes, awhite light source, etc.), which can be broadband light sources, and/ornarrower band light sources. For example, the bandwidth of the lightsource can be selected to provide a range of wavelengths thatfacilitates color imaging at desired wavelengths. Additionally, in someembodiments, light sources 510 can be associated with one or morefilters.

In some embodiments, imaging system 106 can include one or more lightdetectors 512, such as one or more photodiodes, and/or one or more imagesensors (e.g., a CCD image sensor or a CMOS image sensor, either ofwhich may be a single pixel, a linear array, or a two-dimensionalarray). For example, in some embodiments, detectors 512 can include oneor more detectors configured to detect light at specific wavelengths(e.g., using filters, using optics to guide light of differentwavelengths to different portions of the detector(s), etc.)

In some embodiments, imaging system 106 can include one or more opticalconnectors 514. For example, such optical connectors can be fiber opticconnectors configured to form an optical connection between lightsource(s) 510 and/or detector 512 and an optical fiber (e.g., as part ofa fiber optic cable), such as the dual-clad fiber and multimode fibershown in FIG. 2 .

In some embodiments, an OCT imaging system (e.g., OCT imaging device110) can include a hardware processor 218, a user interface and/ordisplay 524, one or more communication systems 526, memory 528, one ormore OCT light sources 530, one or more electromagnetic detectors 532,and/or one or more optical connectors 534. In some embodiments, hardwareprocessor 218 can be any suitable hardware processor or combination ofprocessors, such as a CPU, a GPU, an MCU, an FPGA, an ASIC, a dedicatedimage processor, etc. In some embodiments, input(s) and/or display 524can include any suitable display device(s), such as a computer monitor,a touchscreen, a television, a transparent or semitransparent display, ahead mounted display, etc., and/or input devices and/or sensors that canbe used to receive user input, such as a keyboard, a mouse, atouchscreen, a microphone, a gaze tracking system, motion sensors, etc.Note that, in some embodiments, input(s)/display 524 can be omitted,such as embodiments in which operations of OCT imaging system 110 iscontrolled by computing device 114.

In some embodiments, communications systems 526 can include any suitablehardware, firmware, and/or software for communicating information over acommunication network 502 and/or any other suitable communicationnetworks. For example, communications systems 526 can include one ormore transceivers, one or more communication chips and/or chip sets,etc. In a more particular example, communications systems 526 caninclude hardware, firmware and/or software that can be used to establisha Wi-Fi connection, a Bluetooth connection, a cellular connection, anEthernet connection, an optical connection, etc.

In some embodiments, memory 528 can include any suitable storage deviceor devices that can be used to store instructions, values, etc., thatcan be used, for example, by hardware processor 218 to process imagedata generated by one or more optical detectors, to present contentusing input(s)/display 524, to communicate with computing device 114 viacommunications system(s) 526, etc. Memory 528 can include any suitablevolatile memory, non-volatile memory, storage, any other suitable typeof storage medium, or any suitable combination thereof. For example,memory 528 can include RAM, ROM, EEPROM, one or more flash drives, oneor more hard disks, one or more solid state drives, one or more opticaldrives, etc. In some embodiments, memory 528 can have encoded thereon acomputer program for controlling operation of OCT imaging system 110. Insome such embodiments, hardware processor 218 can execute at least aportion of the computer program to control one or more light sourcesand/or detectors (e.g., to capture OCT data), to generate images and/orcalculate values (e.g., an OCT image, etc.), transmit and/or receiveinformation to/from computing device 114, combine OCT images fromdifferent channels and/or times to generate merged OCT images, etc.

In some embodiments, OCT imaging system 110 can include one or morelight sources 530, such a coherent or incoherent light source (e.g., alight emitting diode or combination of light emitting diodes, a whitelight source, etc.), which can be a broadband light source, or anarrower band light source. For example, the bandwidth of the lightsource can be selected to provide a range of wavelengths thatfacilitates depth detection over a maximum imaging range of OCT imagingsystem 110. Additionally, in some embodiments, light sources 530 can beassociated with one or more filters.

In some embodiments, OCT imaging system 110 can include one or morelight detectors 532, such as one or more photodiodes, and/or one or moreimage sensors (e.g., a CCD image sensor or a CMOS image sensor, eitherof which may be a single pixel, a linear array, or a two-dimensionalarray). For example, in some embodiments, detectors 532 can include oneor more detectors configured to detect light at specific wavelengths(e.g., using filters, using optics to guide light of differentwavelengths to different portions of the detector(s), etc.)

In some embodiments, OCT imaging system 110 can include one or moreoptical connectors 534. For example, such optical connectors can befiber optic connectors configured to form an optical connection betweenlight source(s) 530 and/or detector(s) 532 and an optical fiber (e.g.,as part of a fiber optic cable).

In some embodiments, computing device 114 can include a hardwareprocessor 540, a display 542, one or more inputs 544, one or morecommunication systems 546, and/or memory 548. In some embodiments,hardware processor 540 can be any suitable hardware processor orcombination of processors, such as a CPU, a GPU, an MCU, an FPGA, anASIC, a dedicated image processor, etc. In some embodiments, display 542can include any suitable display devices, such as a computer monitor, atouchscreen, a television, a transparent or semitransparent display, ahead mounted display, etc. In some embodiments, inputs 544 can includeany suitable input devices and/or sensors that can be used to receiveuser input, such as a keyboard, a mouse, a touchscreen, a microphone, agaze tracking system, motion sensors, etc.

In some embodiments, communications systems 546 can include any suitablehardware, firmware, and/or software for communicating information overcommunication network 502 and/or any other suitable communicationnetworks. For example, communications systems 546 can include one ormore transceivers, one or more communication chips and/or chip sets,etc. In a more particular example, communications systems 546 caninclude hardware, firmware and/or software that can be used to establisha Wi-Fi connection, a Bluetooth connection, a cellular connection, anEthernet connection, etc.

In some embodiments, memory 548 can include any suitable storage deviceor devices that can be used to store instructions, values, etc., thatcan be used, for example, by hardware processor 540 to present contentusing display 542, to communication with one or more imaging devices,etc. Memory 548 can include any suitable volatile memory, non-volatilememory, storage, any other suitable type of storage medium, or anysuitable combination thereof. For example, memory 548 can include RAM,ROM, EEPROM, one or more flash drives, one or more hard disks, one ormore solid state drives, one or more optical drives, etc. In someembodiments, memory 548 can have encoded thereon a computer program forcontrolling operation of computing device 114. In such embodiments,hardware processor 540 can execute at least a portion of the computerprogram to receive content (e.g., visible light image data, OCT data)from one or more imaging devices (e.g., color imaging device 106, OCTimaging device 110), co-register visible light image data and OCT imagedata, present content (e.g., images and/or values), transmit content toone or more other computing devices and/or imaging systems, etc.

In some embodiments, computing device 114 can be any suitable computingdevice, such as a general purpose computer or special purpose computer.For example, in some embodiments, computing device 114 can be asmartphone, a wearable computer, a tablet computer, a laptop computer, apersonal computer, a server, etc. As another example, in someembodiments, computing device 114 can be a medical device or a portionof a medical device, a system controller, etc.

FIG. 6 shows an example 600 of a process for generating multimode imagedata in accordance with some embodiments of the disclosed subjectmatter. As shown in FIG. 6 , at 602, process 600 can receive a requestto generate OCT data and visible light image data. In some embodiments,the request can be received using any suitable technique or combinationof techniques. For example, such a request can be received via input toa user interface (e.g., presented by computing device 114, visible lightimaging device 106, and/or OCT imaging device 110). As another example,such a request can be received via actuation of a switch (e.g., aphysical switch that initiates imaging, a software switch that initiatesimaging, a combination of keystrokes on a keyboard that initiatesimagining, etc.).

At 604, process 600 can cause a reflective surface in a probe to beginrotating (e.g., in anticipation of image data being captured). In someembodiments, process 600 can cause the reflective surface to rotateusing any suitable technique or combination of techniques. For example,as described above in connection with FIGS. 4A and 4B, process 600 cancause a motor within a capsule to begin rotating, thereby causing areflective surface that is mechanically coupled to the motor to beginrotating.

At 606, process 600 can cause an OCT light source to emit light towardthe rotating reflective surface via a sample arm of an OCT imagingsystem. In some embodiments, process 600 can use any suitable componentsto cause the light to be emitted toward the reflective surface. Forexample, as described above in connection with FIG. 2 , process 600 cancause light to be emitted from an OCT light source toward a single modefiber that is coupled to the probe via a beam splitter and an opticalcirculator.

At 608, process 600 can cause an OCT light source to emit light toward areference reflector via a reference arm of the OCT imaging system. Insome embodiments, process 600 can use any suitable components to causethe light to be emitted toward the reflective surface. For example, asdescribed above in connection with FIG. 2 , process 600 can cause lightto be emitted from an OCT light source toward a single mode fiber thatis coupled to the reference reflector via the beam splitter and anotheroptical circulator.

At 610, process 600 can detect light returning via the sample arm andthe reference arm to generate OCT data. In some embodiments, process 600can use any suitable technique or combination of techniques to generateOCT data using the returning light from the sample arm and the referencearm. For example, as described above in connection with FIG. 2 , lightfrom the two arms can interfere at an optical component such as a beamsplitter, and interference between the two signals can be detected.

At 612, process 600 can generate OCT image data in real time based onlight returning via the sample arm and the reference arm. In someembodiments, process 600 can use any suitable technique or combinationof techniques to generate OCT image data. For example, based on theinterference pattern(s) detected at 610, process 600 can generate A-linedata indicative of the structure of the sample along the axial direction(e.g., along an axis extending substantially normal to a surface of thecapsule) at a particular lateral location within the sample beingimaged.

At 614, process 600 can cause a visible light source to emit lighttoward the rotating reflective surface. In some embodiments, process 600can use any suitable components to cause the visible light to be emittedtoward the reflective surface. For example, as described above inconnection with FIG. 2 , process 600 can cause light to be emitted froma visible light source toward a dual clad fiber that is coupled to theprobe via a dual clad fiber coupler and a GRIN fiber.

At 616, process 600 can detect visible light returning from the probethat has been reflected by the sample. In some embodiments, process 600can use any suitable technique or combination of techniques to generatevisible light image data using the returning light. For example, asdescribed above in connection with FIG. 2 , light returning from theprobe can be emitted toward one or more visible light detectors that candetermine an amount of one or more wavelengths of light that have beenreflected by the sample.

At 618, process 600 can generate visible light image data in real timebased on visible light returning from the probe. In some embodiments,process 600 can use any suitable technique or combination of techniquesto generate OCT image data. For example, based on the light detected at616, process 600 can generate color image data for one or more locationson a surface of the sample.

At 620, process 600 can present OCT and/or visible light images based onthe OCT image data generated at 612 and/or the visible light image datagenerated at 618. In some embodiments, process 600 can present the imagedata using any suitable technique or combination of techniques. Forexample, process 600 can present OCT image data and visible light imagedata representing the same portion of the sample in a side-by-sidefashion (e.g., as described below in connection with FIGS. 7B to 7D, 8A,and 8B). As another example, process 600 can present a composite of OCTimage data and visible light image data. In a more particular example,process 600 can present an oblique angle of the sample with the visiblelight image data used to present a surface of the tissue, and the OCTimage data used to present a structure of the sample below the surfaceof the tissue.

FIG. 7A shows an example of a visible light image captured ex vivo ofswine mesenteric vessels generated using a conventional camera.

FIG. 7B shows an example of a visible light image captured ex vivo ofswine mesenteric vessels generated using a capsule-based multimodeendoscopy system implemented in accordance with some embodiments of thedisclosed subject matter. As can be appreciated by a comparison of FIGS.7A and 7B, the implemented capsule-based multimode endoscopy system (animage of which is shown in FIG. 4C) produced visible light image datathat was of comparable or better quality than the conventional whitelight camera, while scanning individual points of the surface. FIG. 7Cshows an example of enface OCT image data captured ex vivo of swinemesenteric vessels generated using a capsule-based multimode endoscopysystem implemented in accordance with some embodiments of the disclosedsubject matter. This shows the surface features that can be generatedusing OCT data alone, and lacks some of the details shown in FIG. 7B.

FIG. 7D shows an example of B-scan OCT image data captured ex vivo ofswine mesenteric vessels generated using a capsule-based multimodeendoscopy system implemented in accordance with some embodiments of thedisclosed subject matter.

FIGS. 8A and 8B show an example of a visible light image andcross-sectional OCT image data, respectively, captured in vivo of swineesophagus generated using a capsule-based multimode endoscopy systemimplemented in accordance with some embodiments of the disclosed subjectmatter. The implemented capsule was also used to image swine esophagusin vivo. The capsule was deployed in swine stomach using a modifiedendoscope which could hold and release the capsule at the distal tip, astep that is unnecessary in humans since an unsedated subject cantypically swallow the capsule which will slide down to the stomach dueto peristalsis. The swine esophagus was imaged using the implementedcapsule-based multimode endoscopy system (an image of which is shown inFIG. 4C) by pulling back the capsule at a constant speed using amotorized pullback device while OCT and visible light image data wasgenerated. In some embodiments, a constant pullback speed may bedesirable, as it facilitates easier reconstruction of the tissue imagein a correct form factor. Within the visible light image of FIG. 8A,blood vessels on the esophagus surface can be clearly identified, whilein the OCT image different layers of esophagus can be observed.

In some embodiments, any suitable computer readable media can be usedfor storing instructions for performing the functions and/or processesdescribed herein. For example, in some embodiments, computer readablemedia can be transitory or non-transitory. For example, non-transitorycomputer readable media can include media such as magnetic media (suchas hard disks, floppy disks, etc.), optical media (such as compactdiscs, digital video discs, Blu-ray discs, etc.), semiconductor media(such as RAM, Flash memory, electrically programmable read only memory(EPROM), electrically erasable programmable read only memory (EEPROM),etc.), any suitable media that is not fleeting or devoid of anysemblance of permanence during transmission, and/or any suitabletangible media. As another example, transitory computer readable mediacan include signals on networks, in wires, conductors, optical fibers,circuits, any other suitable media that is fleeting and devoid of anysemblance of permanence during transmission, and/or any suitableintangible media.

It will be appreciated by those skilled in the art that while thedisclosed subject matter has been described above in connection withparticular embodiments and examples, the invention is not necessarily solimited, and that numerous other embodiments, examples, uses,modifications and departures from the embodiments, examples and uses areintended to be encompassed by the claims attached hereto. The entiredisclosure of each patent and publication cited herein is herebyincorporated by reference, as if each such patent or publication wereindividually incorporated by reference herein.

Various features and advantages of the invention are set forth in thefollowing claims.

What is claimed is:
 1. A probe, comprising: a rigid capsule; a flexible tether coupled to a proximal end of the capsule; a rotatable reflective surface disposed within the capsule; a static first lens disposed within the capsule; a first optical fiber optically coupled to the first lens, the first optical fiber passing through the flexible tether; a second optical fiber optically coupled to the first lens, the second optical fiber passing through the flexible tether; and a second lens disposed between a distal end of the second optical fiber and the first lens, the second lens optically coupled to the second optical fiber and the first lens.
 2. The probe of claim 1, wherein the rotatable reflective surface is configured to receive light emitted by the first lens and direct the light toward a circumference of the rigid capsule.
 3. The probe of claim 1, further comprising a spacer disposed between the first lens and the second lens.
 4. The probe of claim 1, wherein the first optical fiber is a single mode fiber that is configured to be optically coupled to an optical coherence tomography imaging system.
 5. The probe of claim 4, wherein the second optical fiber is a dual clad fiber that is configured to be optically coupled to a visible light imaging system.
 6. The probe of claim 1, further comprising a motor that is mechanically coupled to the rotatable reflective surface, and configured to rotate the rotatable reflective surface.
 7. The probe of claim 1, wherein the first optical fiber is adjacent and parallel to the second optical fiber, and wherein the first optical fiber and the second optical fiber are configured to couple to separate imaging systems.
 8. The probe of claim 1, wherein the first lens comprises a ball lens.
 9. The probe of claim 8, wherein the ball lens has an axial diameter of between 0.1 and 5 millimeters (mm).
 10. The probe of claim 1, wherein the second lens comprises a graded index fiber.
 11. The probe of claim 10, wherein the graded index fiber has a length of between 100 and 1,000 micrometers (μm).
 12. The probe of claim 11, wherein there is no graded index fiber between the first optical fiber and the first lens.
 13. The probe of claim 1, wherein a first electromagnetic radiation emitted from the first optical fiber is transmitted through the first lens to a sample, and wherein a second electromagnetic radiation received from the sample is transmitted through the first lens and the second lens into the second optical fiber.
 14. The probe of claim 1, wherein a first electromagnetic radiation emitted from the first optical fiber is transmitted through the first lens to a sample, and wherein a second electromagnetic radiation emitted from the second optical fiber is transmitted through the second lens and the first lens.
 15. A system for capsule-based multimode endoscopy, comprising: a visible light imaging system comprising: a visible light source; and a visible light detector; an optical coherence tomography (OCT) imaging system comprising: an OCT light source; an OCT detector; a sample arm optically coupled to the OCT light source and the OCT detector; and a reference arm optically coupled to the OCT light source and the OCT detector, the reference arm comprising a reference reflector; and a probe comprising: a rigid capsule; a flexible tether coupled to a proximal end of the capsule; a rotatable reflective surface disposed within the capsule; a first lens disposed within the capsule; a first optical fiber optically coupled to the first lens and the sample arm of the OCT imaging system, the first optical fiber passing through the flexible tether; a second optical fiber optically coupled to the first lens and the visible light imaging system, the second optical fiber passing through the flexible tether; and a second lens disposed between a distal end of the second optical fiber and the first lens, the second lens optically coupled to the second optical fiber and the first lens.
 16. The system of claim 15, further comprising: at least one processor that is programmed to: cause the rotatable reflective surface to rotate; cause the OCT light source to emit light toward the rotatable reflective surface via the first optical fiber; cause the visible light source to emit light toward the rotatable reflective surface via the second optical fiber; generate OCT data based on an interference between light reflected from a sample and light reflected from the reference reflector; generate visible light image data based on light reflected from a surface of the sample; and cause an image representing a first portion of the sample based on the OCT data to be presented simultaneously with an image representing the first portion of the sample based on the visible light image data.
 17. The system of claim 15, wherein the rotatable reflective surface is configured to receive light emitted by the first lens and direct the light toward a circumference of the rigid capsule.
 18. The system of claim 15, wherein the probe further comprises a spacer disposed between the first lens and the second lens.
 19. The system of claim 15, wherein the first optical fiber is a single mode fiber.
 20. The system of claim 19, wherein the second optical fiber is a dual clad fiber, and wherein a core of the dual clad fiber is optically coupled to the visible light source and a cladding of the dual clad fiber is optically coupled to the visible light detector.
 21. The system of claim 15, wherein the probe further comprises a motor that is mechanically coupled to the rotatable reflective surface, and configured to rotate the rotatable reflective surface.
 22. The system of claim 15, wherein at least one of the first optical fiber or the second optical fiber is disposed off of a central axis of the first lens.
 23. The system of claim 15, wherein the first optical fiber is disposed on a central axis of the first lens and the second optical fiber is disposed off of the central axis of the first lens.
 24. The system of claim 15, wherein the first lens comprises a ball lens.
 25. The system of claim 24, wherein the ball lens has an axial diameter of between 0.1 and 5 millimeters (mm).
 26. The system of claim 15, wherein the second lens comprises a graded index fiber.
 27. The system of claim 26, wherein the graded index fiber has a length of between 100 and 1,000 micrometers (μm).
 28. The system of claim 27, wherein there is no graded index fiber between the first optical fiber and the first lens.
 29. The system of claim 15, wherein a first electromagnetic radiation emitted from the first optical fiber is transmitted through the first lens to a sample, and wherein a second electromagnetic radiation received from the sample is transmitted through the first lens and the second lens into the second optical fiber.
 30. The system of claim 15, wherein a first electromagnetic radiation emitted from the first optical fiber is transmitted through the first lens to a sample, and wherein a second electromagnetic radiation emitted from the second optical fiber is transmitted through the second lens and the first lens. 